通讯机构：
[Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
Cholesterol transport system;Atherosclerosis;High-density lipoprotein
摘要：
Atherosclerosis, the pathological basis of most cardiovascular disease (CVD), is closely associated with cholesterol accumulation in the arterial intima. Excessive cholesterol is removed by the reverse cholesterol transport (RCT) pathway, representing a major antiatherogenic mechanism. In addition to the RCT, other pathways are required for maintaining the whole-body cholesterol homeostasis. Thus, we propose a working model of integrated cholesterol transport, termed the cholesterol transport system (CTS), to describe body cholesterol metabolism. The novel model not only involves the classical view of RCT but also contains other steps, such as cholesterol absorption in the small intestine, low-density lipoprotein uptake by the liver, and transintestinal cholesterol excretion. Extensive studies have shown that dysfunctional CTS is one of the major causes for hypercholesterolemia and atherosclerosis. Currently, several drugs are available to improve the CTS efficiently. There are also several therapeutic approaches that have entered into clinical trials and shown considerable promise for decreasing the risk of CVD. In recent years, a variety of novel findings reveal the molecular mechanisms for the CTS and its role in the development of atherosclerosis, thereby providing novel insights into the understanding of whole-body cholesterol transport and metabolism. In this review, we summarize the latest advances in this area with an emphasis on the therapeutic potential of targeting the CTS in CVD patients.
摘要：
Atherosclerosis is a chronic disease characterized by the deposition of excessive cholesterol in the arterial intima. Macrophage foam cells play a critical role in the occurrence and development of atherosclerosis. The generation of these cells is associated with imbalance of cholesterol influx, esterification and efflux. CD36 and scavenger receptor class A (SR-A) are mainly responsible for uptake of lipoprotein-derived cholesterol by macrophages. Acyl coenzyme A:cholesterol acyltransferase-1 (ACAT1) and neutral cholesteryl ester hydrolase (nCEH) regulate cholesterol esterification. ATP-binding cassette transporters A1 (ABCA1), ABCG1 and scavenger receptor BI (SR-BI) play crucial roles in macrophage cholesterol export When inflow and esterification of cholesterol increase and/or its outflow decrease, the macrophages are ultimately transformed into lipid-laden foam cells, the prototypical cells in the atherosclerotic plague. The aim of this review is to describe what is known about the mechanisms of cholesterol uptake, esterification and release in macrophages. An increased understanding of the process of macrophage foam cell formation will help to develop novel therapeutic interventions for atherosclerosis. (c) 2013 The Authors. Published by Elsevier B.V. All rights reserved.
